A Sneak Peek Into Future Testing For Multiple Sclerosis

Doctors may soon be able to use blood tests to predict how primary progressive multiple sclerosis (PPMS) will worsen overtime for patients.¹ This opens the door to earlier interventions and personalized treatment plans, eventually creating opportunities to slow the progression of the disease.

Primary progressive multiple sclerosis is a specific type of multiple sclerosis (MS) where symptoms steadily worsen over time from the start of the illness. This is different from other multiple sclerosis types where there may be periods of relapse (symptom flare-ups) and remission (reduced symptoms).²  

Scientists have made progress in identifying biomarkers to predict the course of multiple sclerosis, but they still need to find better options that are specifically tailored to people with the progressive form of the disease.

Luckily, Dr. Manuel Comabella, from the Multiple Sclerosis Center of Catalonia (Cemcat), along with a global team of scientists, are working on exactly that. Their study, published in Journal of Neurology, Neurosurgery and Psychiatry, reports which MS-related markers can be measured in the blood to predict how primary progressive multiple sclerosis disability will worsen over time.

They found that simply measuring NfL, GFAP, and CHI3L1 protein levels in the blood could predict disability changes in patients with primary progressive multiple sclerosis. Increasing protein levels correlated with increased disability scores, and this relationship seemed to hold true within 6 and 10 years of the initial test.

The decade-long investigation

The researchers followed 141 patients with primary progressive multiple sclerosis from 18 different European MS centers over ten years. The aim was to find out whether measuring three known biomarkers for MS :neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and chitinase 3-like 1 (CHI3L1), could be used to predict how quickly a patient’s disability worsens.^4-6 

Patients were divided into two groups: those with inflammation and those without. Patients in the inflammatory group had at least one of the following: a relapse within 3 months of initial testing, active lesions (seen on MRI) near the time of testing, or new active lesions appearing on MRI scans during follow-up care. Patients in the non-inflammatory group had none of the aforementioned signs at any point during the study.

They measured the patient’s blood markers and disability status at the start of the study, then again after 2, 6, and almost 10 years.¹ They used a common evaluation method called EDSS to measure disability in multiple sclerosis. The EDSS gauges walking difficulties, bladder and bowel issues, vision and balance problems, swallowing and speech difficulties, numbness, muscle function, and memory and thinking. The scale ranges from 0 to 10 in 0.5 unit increments. The higher the score, the greater the disability.⁷

Understanding the connection

Can tracking MS biomarker levels forecast how quickly someone’s primary progressive multiple sclerosis is getting worse? To answer this, the scientists first needed to figure out if there’s a clear connection between the biomarkers and how fast the disease worsens.

At the start of the study, the measured Nfl, GFAP, and CHI3L1 proteins in participants’ blood were at “average” levels. Their EDSS scores averaged at a 4, meaning there was significant disability but participants could walk without aid for about 500 meters (547 yards), and they could be up and about for about 12 hours a day. What does this mean? While the biomarker results give some insight into the condition of the patients, it doesn’t exactly show how severe someone’s MS is at that moment, and it doesn’t explain any differences between someone who was recently diagnosed with MS versus someone who has had it for years.

Excitingly, after year two of the study, the scientists found their answer: doubling of the initial NfL, GFAP, and CHI3L1 levels related to increases in EDSS scores. Every time the biomarker measurements doubled in the study, there was a corresponding increase (around 0.1 points) in the disability score. This finding hints at a link between the markers and a patient’s disability. An increase of just 0.3 points for a disability score can have a big impact on someone’s daily life. For example, it could mean they can no longer walk, even short distances, without help. 

The biomarker-disability correlation was similar at the six-year and ten-year marks. Interestingly, in the non-inflammatory patient group, increases in the CHI3L1 protein was consistently linked to worsening disability over time.

What’s next?

This study is exciting news because it shows that the biomarkers already helpful for other forms of MS could work for diagnosing and tracking primary progressive multiple sclerosis too! 

Traditional methods of tracking multiple sclerosis progression (MRI and spinal tap) can be complex and uncomfortable for patients. But blood tests measuring the markers in this study would be a simpler, cheaper, and less invasive option for patients. Most importantly, they can help assess primary progressive multiple sclerosis progression over time, allowing doctors to start preventative measures sooner.¹

More testing and clinical trials are now needed to move this idea forward and develop the blood tests as a new primary progressive multiple sclerosis diagnostic tool. 

References

1. Fissolo N, Benkert P, Sastre-Garriga J, et al. Serum biomarker levels predict disability progression in patients with primary progressive multiple sclerosis. Journal of Neurology, Neurosurger & Psychiatry. Published online November 8, 2023. doi:https://doi.org/10.1136/jnnp-2023-332251
2. “How Is Multiple Sclerosis Diagnosed?” National Multiple Sclerosis Society, www.nationalmssociety.org/Symptoms-Diagnosis/Diagnosing-MS. Accessed 17 Apr. 2024.
3. “Primary Progressive Multiple Sclerosis (PPMS).” National Multiple Sclerosis Society, www.nationalmssociety.org/What-is-MS/Types-of-MS/Primary-progressive-MS#section-2. Accessed 22 Apr. 2024. 
4. Gaetani L, Blennow K, Calabresi P, Di Filippo M, Parnetti L, Zetterberg H. Neurofilament light chain as a biomarker in neurological disorders. Journal of Neurology, Neurosurgery & Psychiatry. 2019;90(8):870-881. doi:https://doi.org/10.1136/jnnp-2018-320106
5. Yang Z, Wang KKW. Glial Fibrillary acidic protein: From intermediate filament assembly and gliosis to neurobiomarker. Trends in neurosciences. 2015;38(6):364-374. doi:https://doi.org/10.1016/j.tins.2015.04.003
6. Yu JE, Yeo IJ, Han SB, et al. Significance of chitinase-3-like protein 1 in the pathogenesis of inflammatory diseases and cancer. Experimental & Molecular Medicine. 2024;56(1):1-18. doi:https://doi.org/10.1038/s12276-023-01131-9
7. “Expanded Disability Status Scale (EDSS).” Multiple Sclerosis Society UK, www.mssociety.org.uk/about-ms/treatments-and-therapies/getting-treatment-for-ms/expanded-disability-status-scale#:~:text=The%20Expanded%20Disability%20Status%20Scale%20(EDSS)%20is%20a%20way%20of,3.5%2C%204%20and%20so%20on. Accessed 23 Apr. 2024.